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Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy


Zattoni, M. Brain infiltration of leukocytes contributes to the pathophysiology of temporal lobe epilepsy. 2010, University of Zurich, Faculty of Medicine.

Abstract

Temporal lobe epilepsy (TLE) is a chronic neurological disorder with a world-wide global incidence of 0.5-2%. Despite the wealth of studies on the functional and morphological alterations occuring in TLE, the pathophysiology of this disorder remains poorly understood. A paradigm shift was introduced by recent experimental and clinical data suggesting that inflammation directly contributes to the pathogenesis of epilepsy. The aim of this project is based on our own observations that several pro-inflammatory genes are upregulated both in brain tissue and microvascular endothelial cells obtained from patients with intractable TLE, and that CD45+ leukocytes can infiltrate the epileptic brain parenchyma. To understand the relevance of these findings, we investigated wether interactions between innate and adaptive immunity underlie neurodegeneration of the hippocampal formation and epileptogenesis in an experimental model of focal epilepsy. While several animal models of TLE are available, they often presentwith bilateral lesions underlying generalized seizures, as seen in the "pilocarpine model", for instance.
To overcome these major differences with the human pathology, a mouse model has been developed, based on a unilateral injection of a low dose kainic acid (KA) into the dorsal hippocampus of adult mice. In this model, an epileptic focus develps gradually, accompanied by severe degeneration of the CA1 region and a pronounced dispersion of granuel sells in the dentate gyrus. [...]

Abstract

Temporal lobe epilepsy (TLE) is a chronic neurological disorder with a world-wide global incidence of 0.5-2%. Despite the wealth of studies on the functional and morphological alterations occuring in TLE, the pathophysiology of this disorder remains poorly understood. A paradigm shift was introduced by recent experimental and clinical data suggesting that inflammation directly contributes to the pathogenesis of epilepsy. The aim of this project is based on our own observations that several pro-inflammatory genes are upregulated both in brain tissue and microvascular endothelial cells obtained from patients with intractable TLE, and that CD45+ leukocytes can infiltrate the epileptic brain parenchyma. To understand the relevance of these findings, we investigated wether interactions between innate and adaptive immunity underlie neurodegeneration of the hippocampal formation and epileptogenesis in an experimental model of focal epilepsy. While several animal models of TLE are available, they often presentwith bilateral lesions underlying generalized seizures, as seen in the "pilocarpine model", for instance.
To overcome these major differences with the human pathology, a mouse model has been developed, based on a unilateral injection of a low dose kainic acid (KA) into the dorsal hippocampus of adult mice. In this model, an epileptic focus develps gradually, accompanied by severe degeneration of the CA1 region and a pronounced dispersion of granuel sells in the dentate gyrus. [...]

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Additional indexing

Item Type:Dissertation
Referees:Fritschy J M, Frei K, Verrey F
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Clinic for Neurosurgery
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2010
Deposited On:09 Jun 2011 11:28
Last Modified:07 Dec 2017 08:26

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